Expression of Sertoli Cell Junctional Proteins in the Testis.
Salian S, Doshi T, Vanage G.
Toxicology. 2009 Sep 24. [Epub ahead of print]
National Center for Preclinical Reproductive and Genetic Toxicology,
National Institute for Research in Reproductive Health (ICMR), J M Street,
Parel, Mumbai, 400 012, Maharashtra, India.
BACKGROUND: Sertoli cell junctional proteins (SCJP) (viz. adhesion, gap and
tight junctions) are important for spermatogenesis and perturbations in
expression of these proteins are associated with impairments in process of
sperm production. Bisphenol A (BPA) is an endocrine disrupter that has been
associated with impaired spermatogenesis. However the mechanistic basis of
impaired spermatogenesis is unknown, whether BPA is a Sertoli cell toxicant
has not yet been fully investigated.
OBJECTIVES: The present study was undertaken to decipher the effects of
neonatal exposure of male rats to BPA on fertility and its effect on the
testicular expression of SCJP during development.
METHODS: Neonatal male rats were s.c. injected with BPA at doses ranging
from 0.6-10mug/rat (100-1600mug/kg bw of BPA) on postnatal days (PNDs) 1-5,
and controls received vehicle. DES was used as a positive control. Male
fertility was assessed during adulthood and the lowest dose of BPA that was
most effective at impairing fertility was determined. Immunohistochemical
localization for Connexin 43 (Cx-43, gap junctional), Zona Occludin-1 (ZO-1,
tight junctions) and N-cadherin (adherens junction) was carried out on
testicular tissue sections obtained from PNDs 15, 30, 45 and 90 of rats
exposed to lowest dose of BPA that impaired fertility.
RESULTS: Females mated with male rats that were exposed neonatally to
various concentrations of BPA showed a significant increase in
post-implantation loss and a decrease in litter size. There were significant
changes in sperm count along with hormonal imbalances in the rats exposed
neonatally to BPA. The 2.4mug dose (400mug/kg bw) of BPA was determined as
the lowest dose that was capable of impairing male fertility. A significant
reduction in the expression of Cx-43 (PND 45 and 90) and increases in the
expression of N-cadherin (PND 45 and 90) and ZO-1(PND 90) were observed in
the testes of rats exposed neonatally to effective dose of BPA.
Interestingly, there was an altered expression pattern of Cx43 amongst the
sloughed cells in the testes of the experimental rats as compared to
controls.
CONCLUSION: Neonatal exposure of BPA to rats impairs their fertility and has
the potential to induce perturbations in SCJP. These perturbations may be
one of the contributing factors that lead to impairments in spermatogenesis
in the exposed animals and can be used as potential biomarkers to study BPA-
induced effects on testes.
PMID: 19782717 [PubMed - as supplied by publisher]
